1. Definition and Epidemiology
- Definition: An age-dependent epileptic encephalopathy occurring in infancy.
- West Syndrome Triad:
- Infantile Spasms: Unique seizure type (clusters of flexor/extensor jerks).
- Hypsarrhythmia: Pathognomonic interictal EEG pattern.
- Developmental Regression: Arrest or regression of psychomotor development.
- Peak Onset: 3 to 7 months of age (90% onset < 1 year).
2. Etiology (Classification)
Currently classified into Structural/Metabolic (Symptomatic) and Unknown (Cryptogenic).
| Category | Common Causes |
|---|---|
| Structural (Most Common) | Tuberous Sclerosis Complex (TSC) (Major cause), Hypoxic-Ischemic Encephalopathy (HIE), Neurofibromatosis 1, Cortical Dysplasia, Lissencephaly, Aicardi Syndrome. |
| Metabolic | Phenylketonuria (PKU), Non-ketotic hyperglycinemia, Pyridoxine dependency, Mitochondrial disorders. |
| Genetic | ARX and CDKL5 mutations; Trisomy 21. |
| Unknown | No cause identified despite investigation (better prognosis). |
3. Clinical Features (Semiology)
- The Spasm: Sudden, brief (1–2 sec) contraction of axial and limb muscles followed by a tonic phase (less than 10 sec).
- Flexor (Salaam attacks): Flexion of neck, trunk, and adduction of arms (most common).
- Extensor: Extension of neck and trunk.
- Mixed: Elements of both.
- Timing: Characteristically occur in clusters (dozens per cluster), most frequently on awakening or falling asleep. Rarely occur during sleep.
- Associated Signs: Cry or laugh after the spasm; eye deviation; autonomic changes (flushing/pallor).
4. Investigations
- EEG (Gold Standard):
- Interictal: Hypsarrhythmia—chaotic, high-voltage (>200 µV) slow waves with multifocal spikes and sharp waves; lack of synchronization between hemispheres.
- Ictal: High-voltage slow wave followed by voltage attenuation (electrodecremental response).
- Neuroimaging (MRI Brain): Mandatory to identify structural substrates (tubers, malformations).
- Metabolic Screen: If MRI is normal (Tandem Mass Spectrometry, Urine organic acids, Ammonia, Lactate).
- Genetic Testing: Whole Exome Sequencing (WES) or Epilepsy Gene Panels if etiology remains obscure.
5. Management
Early treatment is critical to improve neurodevelopmental outcomes (Lead Time Bias).
A. Pharmacotherapy
| Agent | Indication/Remarks |
|---|---|
| ACTH (Adrenocorticotropic Hormone) | First-line choice for non-TSC cases. Stimulates endogenous steroid production. Dose: High dose vs Low dose (controversial); usually short course (2–4 weeks). Side Effects: Hypertension, infection risk, electrolyte imbalance. |
| Oral Prednisolone | High-dose oral prednisolone (40–60 mg/day) is a cost-effective alternative to ACTH (UKKI Study showed similar efficacy). |
| Vigabatrin | Drug of Choice for Tuberous Sclerosis (TSC). Irreversible GABA-transaminase inhibitor. Side Effect: Concentric visual field constriction (Retinal toxicity) – requires monitoring. |
| Benzodiazepines | Clonazepam/Nitrazepam (Adjunctive/Second line). |
| Pyridoxine (Vit B6) | Trial given to rule out pyridoxine-dependent epilepsy. |
B. Non-Pharmacologic
- Ketogenic Diet: Highly effective in refractory cases or GLUT-1 deficiency.
- Epilepsy Surgery: Focal resection/Hemispherectomy if a discrete resectable lesion (e.g., focal cortical dysplasia) is identified.
6. Prognosis
- Seizure Control: 50–70% respond to hormonal therapy or Vigabatrin.
- Long-term:
- High risk of evolution into Lennox-Gastaut Syndrome (LGS).
- Development: Poor. 70–90% have intellectual disability; high rates of autism.
- Cryptogenic cases have a better prognosis than symptomatic cases.